Disease Summaries

Practical Issues in the Treatment of Acute Asthma in Children

Introduction

Asthma is a common pediatric disease which children often develop by age 5 years. Despite a better understanding of the pathogenesis of asthma and improved treatment, acute exacerbations of asthma continue to cause frequent emergency room visits and hospitalizations. Although office consultations for wheezing and other symptoms of asthma are common, first-time wheezers can present with acute severe asthma. Treatment of acute asthma is addressed in the World Allergy Organization synopsis, "Acute Asthma", by Michael Kaliner and Richard Lockey in this series of Web-based educational programs. However, several practical issues on treating children with acute asthma deserve further consideration.

Differential diagnosis

Various pediatric conditions can mimic asthma, some of which occur concomitantly with asthma while others have a completely different pathophysiological mechanism.

Therefore, an accurate diagnosis is essential before initiating therapy. Physicians caring for children with presumed asthma must be familiar with diseases that present in a similar manner and exclude them from the differential diagnosis before establishing the diagnosis of asthma (Table I).

Table 1: Conditions in children that can mimic or be confused with acute asthma.

Lower airway obstruction

Acute tracheobronchitis
Acute bronchiolitis
Tuberculosis and other granulomatous diseases of the airways
Obstruction from malformations of lower airways, cardiovascular system, gastrointestinal system and the lungs

Vascular rings (e.g. double aortic arch, pulmonary sling)

Duplication of gastrointestinal system

Congenital pulmonary emphysema and other congenital malformations of the lungs

It is important that these diseases be considered in children with persistent wheeze, especially those not responding to treatment. Consultation with an expert in pediatric asthma is usually recommended.

Assessment of severity of acute asthma in children

Initial assessment of the severity of asthma is necessary before treatment is initiated. Once the appropriate level of care is achieved, certain additional points obtained from the history are useful, e.g., duration of attack, degree of exacerbation and triggers which cause exacerbation, such as specific allergens or respiratory tract infections. The longer the attack, the more likely it is that recovery will be prolonged and that more intense therapy is required. Medications used previously should be identified, particularly, the use of inhalational or systemic glucocorticosteroids. The patient may be at risk for severe asthma requiring prolonged and intensive treatment if there is a history of previous hospitalizations, frequent emergency room visits, chronic inhalational or systemic corticosteroid use or recent withdrawal from systemic steroids, and a history of intensive care unit management, with or without mechanical ventilation. Psychosocial problems, particularly in teenagers, are a risk factor for sudden death. A systematic approach and evaluation of the severity of acute asthma is also outlined in the WAO Web synopsis by Kaliner and Lockey and in most clinical practice guidelines (such as the NAEPP-3 and GINA 2008).

Recommendations on severity evaluation are, however, somewhat complicated and difficult to memorize in acute clinical situations. Moreover, not all symptoms and signs in each acute category appear simultaneously, sometimes leading to an inappropriate diagnosis or treatment.

Several clinical scoring systems using salient clinical findings are available for children with acute asthma. These scoring systems are useful since they can be accessed instantaneously and can be recorded onto flow-sheets used for serial evaluation of the patient's asthma, severity, and response to therapy. Examples include Wood's for older and Parkin's for younger children. There are shortcomings for each of these scoring systems. For example, the Wood's clinical asthma score was designed several decades ago when many of the current medications used to treat acute asthma were not available. As a result, some symptoms, such as loss of consciousness, are infrequently encountered today, rendering the scoring system somewhat obsolete for current use. The Parkin's score was designed mainly for use in younger children, particularly those less than 5 years of age and includes some parameters which are difficult to ascertain, such as the inspiratory:expiratory ratio . A study in 2009 by Ducharme et al identified oxygen saturation along with certain clinical signs which correlated with attack severity.

Therefore, the author (PV) selected items easily accessed with good sensitivity to design a scoring system at the Siriraj Hospital in Bangkok to evaluate children with asthma exacerbations. This scoring system was validated and was also found useful for monitoring efficacy of treatment, thus improving communication among physicians and other healthcare professionals caring for these acutely ill patients. Table 2 summarizes the symptoms and severity of clinical findings used in this scoring system.

Peak flow rate (PEF)

The use of a peak flow measurement is not included in the Siriraj Hospital scoring system since most children with severe asthma cannot appropriately blow into a peak flow meter. However, for those with less severe attacks, a PEF measurement is indicated prior to initiation of treatment to help determine attack severity. PEF measurement should be repeated at regular intervals to help guide the response to treatment. Normal PEF values vary with height and a simple formula for calculating normal PEF in children is:
Peak flow rate (in L/min) = (5 x height in cm) - 400
Children presenting with a PEF of less than 25% of predicted have severe asthma and should receive urgent attention.

Initial treatment of acute asthma

Most exacerbations, especially mild cases, can usually be managed in the outpatient setting. However, success for outpatient care should always include a written action plan. Patients who fail to improve and are compliant despite such a plan are probably more severe and may need further evaluation and intervention in a physician's office or emergency department. An algorithm that serves as a basis for the emergency outpatient treatment of acute asthma is illustrated in Figure 1. Details are outlined below.

Oxygen

Most children who present with acute asthma are not oxygen desaturated. However, low flow O2 is indicated for those with a borderline saturation index, (e.g. in the lower 90's) since treatment with beta-agonists can worsen the ventilation-perfusion ratio and decrease the PaO2 level even more. Continuous monitoring of PaO2 is recommended until the patient is stable.

Beta-agonists

Short-acting beta-agonists (SABA) are the mainstay of acute asthma treatment. Three to five puffs of albuterol (100 µg/puff), or its equivalent, via a metered dose inhaler (deliver one puff at a time, followed by 5-10 breaths) through a spacer/mask system is just as effective as is nebulization with the same medication and is less time consuming. However, for those who cannot use a metered dose inhaler and have a severe attack, nebulized albuterol 0.05- 0.15mg/kg/dose [0.5% albuterol nebulizing solution (5mg/ml) - 0.01-0.03 cc/kg, max 5mg/dose] every 20 minutes, with O2 at 2-6 litres flow per minute, is the treatment of choice. For those who do not respond to three consecutive doses of albuterol, delivered 20 minutes apart, inhaled and preferably systemic corticosteroids should be promptly administered and the patient considered for hospitalization and further treatment. For those with a continuous severe attack, continueous nebulization (CN) with beta-agonists is indicated. Systems such as the HEART® (High-output Extended Aerosol Respiratory Therapy) nebulizer system make CN convenient, but this subject is beyond the scope of this synopsis. Interested readers should consult the appropriate reference in the recommended reading list or visit the following website to learn about this mode of therapy: www.carestream.com/uploads/file/Westmed-heartnebs.pdf

Ipratropium bromide

Ipratropium bromide, a quaternary ammonium anticholinergic medication,, has a long duration of action (up to 12 hours) and complements the bronchodilatating effects of albuterol. Existing evidence supports its use with inhaled beta-agonists for acute asthma in children and is effective with very severe exacerbations. The addition of ipratropium decreases rates of hospitalization and duration of stay in the emergency departments although its use among patients admitted to the hospital has not been adequately evaluated. Ipratropium bromide is delivered through nebulization, commonly with albuterol, at dosage of 0.25-0.5 mg q 20 minutes. Such doses are those recommended in various reports in the past (see Systematic reviews of use of anticholinergics in childhood asthma. Rodriogo et al, Thorax 2005:50:740-746). Despite the fact that peak of action of ipratropium occurs at 60 minutes, the drug was given q 20 minutes in some studies.

Theophylline

The use of intravenous theophylline for acute asthma has declined over the last 20 years. However, a Cochrane analysis of theophylline for acute asthma indicates that this agent is effective. The problem is that it can cause serious side-effects and therefore, children treated with IV theophylline need to be managed where theophylline levels can be closely monitored.

The NAEPP -3 expert panel (2007), however, did not recommend the use of theophylline in acute asthma in children despite the fact that a large Australian study suggested that theophylline in children with severe asthma could potentially decrease the need for intubation and mechanical ventilation.

Corticosteroids

Systemic corticosteroids, such as prednisone, prednisolone and methylprednisolone, are indicated in acute asthma in children. Dexamethasone should be avoided because it is a long-acting corticosteroid versus the former, which are intermediate-acting glucocorticosteroids. A single dose of dexamethasone can suppress the hypophyseal- pituitary-adrenal axis for days. Intermediate-acting glucocorticosteroids, such as prednisone, prednisolone, or methylprednisolone, 1-2 mg/kg/day, should be administered in divided doses for 3-5 days or until the patient is stable. Parenteral administration of corticosteroids has not been shown to be more efficacious than oral administration. Thus, oral prednisolone is commonly preferred.

High-dose inhaled corticosteroids (ICS), such as budesonide and fluticasone propionate using doses as high as 2 mg delivered by spacer/mask or nebulization at frequent intervals, have been shown to be effective in some studies of acute asthma in children. However, systemic corticosteroids, given orally or parenterally, are more cost-effective and assure optimal treatment for this potentially life-threatening condition.

Treatment of patients with severe asthma attacks not responding to beta-agonists, and glucocorticosteroids

Beta-agonists and systemic corticosteroids help the large majority of children with acute asthma. However, those who do not respond should be admitted to the hospital for further evaluation and treatment (see Algorithm in Figure 2). For children who present with or develop persistent hypoxemia, exhaustion, or changes in consciousness, admission to the intensive care unit and possible intubation is indicated.

In such a case, a chest x-ray is indicated, particularly if the diagnosis is unclear, or to rule out atelectasis, pulmonary infiltrates, pneumomediastinum, or pneumothorax. These conditions can be suspected, particularly if the physical findings suggest these complications, if the patient is rapidly deteriorating, or gas exchange abnormalities are greater than expected.

Electrolytes and blood gas abnormalities should be determined and corrected as soon as possible. Patients with acute asthma are usually dehydrated and fluids indicated. Administration of continuous nebulization of albuterol is indicated and the heart rate, respiratory rate, blood pressure, fluid input/output, electrolytes and blood glucose and oxygen saturation monitored. The use of sedatives should be avoided, although in some patients sedation is necessary, particularly those who are intubated and on artificial respiration. In such cases, other medications such as ketamine, MgSO4, inhaled anesthetics, or lidocaine are sometimes necessary. Response to these agents varies among patients and is unpredictable. Patients with severe asthma should be treated in collaboration with an intensive care specialist and should be closely monitored. Details of treatment following intubation are beyond the scope of this synopsis and readers are referred to the reference list.

Mechanical ventilation

Approximately 1-2% of asthmatic children admitted to a hospital require mechanical ventilation, a complex situation since the lungs of these children are over expanded and the risk of pneumothorax high (up to 40%). Such patients are ventilated with lower peak inspiratory pressure (PIP) with optimal PEEP (peak end-expiratory pressure) to decrease this risk. PaCO2 is kept at higher than normal, referred to as permissible hypercarbia. These patients can be given ketamine, MgSO4, inhaled anesthetics or lidocaine to facilitate treatment. Patients usually recover within 1-2 days of mechanical ventilation and those who do not respond to treatment should be evaluated for adenovirus, influenza A, Mycoplasma pneumoniae and other infectious agents which cause severe inflammation of the lower airways and prolong treatment. Further evaluation, such as bronchoalveolar lavage and/or lung biopsy, may be required to further differentiate the disease process.

In-hospital care and discharge planning

Asthmatic children can be frequent users of the emergency room. Without a discharge plan for continual care, many patients will be back in the emergency room or be re-hospitalized. Patients should be evaluated for lung function, atopic status, compliance, and ability to properly use their medications. A hospital designed program is indicated and should include evaluating the family's socioeconomic background, ability of the patient and family to afford medications, selection of the right medications, and if necessary, an asthma education program for the patient and family members. This program should include information about the pathophysiology of asthma, prescribed medications, proper inhaler use, and an individual management plan. Identification of a physician who can provide long-term care is necessary, and discharge planning should be carried out with their collaboration. With proper education and treatment, a meaningful rapport will develop between the physician and other healthcare professionals and the patient and patient's family. Future relapses and asthma progression will be minimized, ensuring a more optimal quality of life not only for the patient but also for the family.

Recommended reading

Castro-Rodriguez JA, Rodrigo GJ. Beta-agonist through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis. J Pediatr 2004;145:172-7.

Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax 2005;60:740-746.

Figure 1: Acute exacerbations of asthma in children and emergency department management. Most acutely severe exacerbations of asthma require an extensive course of therapy in a well-equipped physician's office or the emergency department. PEF % baseline refers to the norm for the individual, established by the clinician. This may be percentage predicted based on standardized norms or the patient's personal best.